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Clomiphene Citrate, Estradiol and Sildenafil for Induction of Ovulation in Unexplained Infertility

Phase 1
Completed
Conditions
Female Infertility
Interventions
Drug: Clomid, Respatio and Ethinyl estradiol
Registration Number
NCT03755037
Lead Sponsor
Nesreen Abdel Fattah Abdullah Shehata
Brief Summary

Diagnosis of unexplained infertility is made after the recommended testing fails to reveal any abnormality. The treatment for unexplained infertility is empiric because it does not address a specific defect or functional impairment. The principal treatments for unexplained infertility include expectant observation with timed intercourse and lifestyle changes, clomiphene citrate and intrauterine insemination (IUI), controlled ovarian hyperstimulation (COH) with IUI, and IVF).

Detailed Description

Clomiphene citrate has been widely used alone, and in combination with intrauterine insemination (IUI), for treatment of unexplained subfertility, The mechanism of action is based on its mixed estrogenic and antiestrogenic properties. Clomiphene is frequently used to treat unexplained female infertility by inducing multifollicular response and correcting potential subtle ovulatory dysfunction .,)The American Society for Reproductive Medicine,2003).

The use of clomiphene citrate decreases the uterine blood flow during the early luteal phase, a periimplantation stage., )The American College of Obstetricians and Gynecologists,1995).

Although ovulation is found in 80% of women with a cumulative effect in 6-8 months, the pregnancy rate can still be very low in these women . The possible causes are the anti-estrogenic effects of CC at the endometrium and cervical mucus level . The endometrial effect is without doubt one of the most important handicaps in infertility treatment. The pregnancy rate can be very low, especially if the endometrial thickness (ET) is \<6-8 mm ., )J Turk Ger Gynecol Assoc. ,2012).

Ethinyl E2 reverse the deleterious effect of CC on endometrial development during the follicular phase. Endometrial thickness was dependent on peak E2 concentrations in serum.,(Richard P. Dickey, et.al.,2003).

Sildenafil citrate could lead to an improvement in uterine blood flow and, in conjunction with estrogen, led to the estrogen-induced proliferation of the endometrial lining .

Sildenafil citrate enhances uterine blood flow and increases endometrial thickening . The achieved implantation depends on the blastocyst's ability to infiltrate the endometrium and develop a sustaining blood supply, which requires the following genes to produce the necessary proteins for digesting the endometrial cellular matrix, to regulate cell growth, and to induce angiogenesis (Razieh Dehghani Firouzabadi,et.al.,2013).

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
150
Inclusion Criteria
  • Women whose infertility tests were normal then diagnosed as unexplained infertility.
Exclusion Criteria
  • Any cause of infertility male factor, tubal or ovarian.
  • Chronic illness as cardiac or renal disease
  • Any contraindication for used drugs

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Estradiol and ccClomid, Respatio and Ethinyl estradiolGroup 1 received estradiol, cc and placebo simillar to sildenafil for induction of ovulation. CC 50 mg (clomid) orally twice daily from 3rd day to 7th day of menstrual cycle of the patient then ethinyl estradiol 0.05mg orally twice daily on the 8th day of same cycle till 11th day.
Sildenafil and ccClomid, Respatio and Ethinyl estradiolGroup 2 received CC 50 mg (clomid) orally twice daily from 3rd day to 7th day of menstrual cycle of the patient, sildenafil citrate (Respatio) 20 mg tab orally 3 times daily from8th day of same cycle till 11th day and placebo simillar to estradiol.
Placebo and ccClomid, Respatio and Ethinyl estradiolGroup 3 received cc and placebo similar to sildenafil and placebo similar to estradiol with the same doses.
Primary Outcome Measures
NameTimeMethod
Ultrasound parametersat day 14 until day 17 of menstrual cycle

Number of follicles in each ovary and endometrial thickness

Secondary Outcome Measures
NameTimeMethod
Pregnancyat day 21 and 24 of menstrual cycle

A serum pregnancy test was done

Trial Locations

Locations (1)

Nesreen Abd El Fattah Abd Allah

🇪🇬

Cairo, Egypt

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